tbuckley/cabot-search huggingface dataset:
Racism and the Textures of Visibility
Authors: Melissa S. Creary
Journal: The American Journal of Bioethics (2023)

"Racism and the Textures of Visibility." The American Journal of Bioethics, 23(7), pp. 109–110This article refers to:Bounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision Medicine Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Use of Real-World Data in Population Science to Improve the Prevention and Care of Diabetes-Related Outcomes
Authors: Edward W. Gregg, Elisabetta Patorno, Andrew J. Karter, Roopa Mehta, Elbert S. Huang, Martin White, Chirag J. Patel, Allison T. McElvaine, William T. Cefalu, Joseph Selby, Matthew C. Riddle, Kamlesh Khunti
Journal: Diabetes Care (2023)

The past decade of population research for diabetes has seen a dramatic proliferation of the use of real-world data (RWD) and real-world evidence (RWE) generation from non-research settings, including both health and non-health sources, to influence decisions related to optimal diabetes care. A common attribute of these new data is that they were not collected for research purposes yet have the potential to enrich the information around the characteristics of individuals, risk factors, interventions, and health effects. This has expanded the role of subdisciplines like comparative effectiveness research and precision medicine, new quasi-experimental study designs, new research platforms like distributed data networks, and new analytic approaches for clinical prediction of prognosis or treatment response. The result of these developments is a greater potential to progress diabetes treatment and prevention through the increasing range of populations, interventions, outcomes, and settings that can be efficiently examined. However, this proliferation also carries an increased threat of bias and misleading findings. The level of evidence that may be derived from RWD is ultimately a function of the data quality and the rigorous application of study design and analysis. This report reviews the current landscape and applications of RWD in clinical effectiveness and population health research for diabetes and summarizes opportunities and best practices in the conduct, reporting, and dissemination of RWD to optimize its value and limit its drawbacks.
The Dialectics of Racial Invisibility and Hyper-Visibility under the <i>Mestizaje</i> Discourse in Latin America
Authors: Constanza P. Silva Gallardo, Tomás González Zarzar
Journal: The American Journal of Bioethics (2023)

"The Dialectics of Racial Invisibility and Hyper-Visibility under the Mestizaje Discourse in Latin America." The American Journal of Bioethics, 23(7), pp. 111–112This article refers to:Bounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision Medicine Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
What Constitutes Ethical Engagement with Africa and the Global South?
Authors: Anye-Nkwenti Nyamnjoh, Cornelius Ewuoso
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Promoting Equality in the Governance of Heritable Human Genome Editing through Ubuntu: Reflecting on a South African Public Engagement Study Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
The Other Side of the Self-Advocacy Coin: How For-Profit Companies Can Divert the Path to Justice in Rare Disease
Authors: Emily Bonkowski, Hadley Stevens Smith
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Innovating for a Just and Equitable Future in Genomic and Precision Medicine ResearchThis article refers to:Rare Disease, Advocacy and Justice: Intersecting Disparities in Research and Clinical Care DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Poor visibility of retracted articles: a problem that should no longer be ignored
Authors: Christophe Boudry, Katherine Howard, Frederic Mouriaux
Journal: BMJ (2023)

from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Getting It Right: How Public Engagement Might (and Might Not) Help Us Determine What Is Equitable in Genomics and Precision Medicine
Authors: Sara Chandros Hull, Lawrence C. Brody, Rene Sterling
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Rare Disease, Advocacy and Justice: Intersecting Disparities in Research and Clinical CareThe Promise and Reality of Public Engagement in the Governance of Human Genome Editing ResearchIs It Just for a Screening Program to Give People All the Information They Want?Bounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision MedicinePromoting Equality in the Governance of Heritable Human Genome Editing through Ubuntu: Reflecting on a South African Public Engagement Study ACKNOWLEDGMENTSThe authors thank their colleagues at NIH for providing critical feedback on this commentary.Additional informationFundingThis work was supported in part by the Intramural Research Programs of the National Human Genome Research Institute.
Hypervisibility, Surveillance, and Bounded Justice through Data-Driven Health Equity Efforts
Authors: Paige Nong, Sarah El-Azab
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Bounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision Medicine DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Narrative Equity in Genomic Screening at the Population Level
Authors: Rosemarie Garland-Thomson, S. A. Larson
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Innovating for a Just and Equitable Future in Genomic and Precision Medicine ResearchThis article refers to:Is It Just for a Screening Program to Give People All the Information They Want? Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
When Less is More: Lessons for Expanded Carrier Screening from Newborn Sequencing Research
Authors: Josephine Johnston
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Is It Just for a Screening Program to Give People All the Information They Want? DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis commentary draws on research supported by the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health & Human Development and the National Human Genome Research Institute under award U19HD077627. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH.
From Community-Based Carrier Programs to Opportunistic Carrier Screening: How the Objective of Carrier Screening Was Lost in Translation
Authors: Anne-Marie Laberge
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Is It Just for a Screening Program to Give People All the Information They Want? DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was supported by a Senior Clinician-Scientist grant from the Fonds de recherche du Québec – Santé (FRQS) and a project grant from the Canadian Institutes of Health Research (CIHR).
Who Is Responsible for Promoting Equity in Rare Disease Research?
Authors: Matthew S. McCoy
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Rare Disease, Advocacy and Justice: Intersecting Disparities in Research and Clinical Care DISCLOSURE STATEMENTDr. McCoy's spouse is employed by the Leukemia & Lymphoma Society.Additional informationFundingThis study was funded by Greenwall Foundation.
Unbounding ELSI: The Ongoing Work of Centering Equity and Justice
Authors: Chessa Adsit-Morris, Rayheann NaDejda Collins, Sara Goering, James Karabin, Sandra Soo-Jin Lee, Jenny Reardon
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Promise and Reality of Public Engagement in the Governance of Human Genome Editing ResearchBounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision Medicine ACKNOWLEDGEMENTSWe would like to acknowledge the support and critical feedback from members of the Leadership in the Ethical and Equitable Design (LEED) of STEM initiative, which include the authors of this piece as well as Mildred K. Cho, Malia Fullerton, Evelynn Hammonds, and Aaron Panofsky. Many of the ideas in this piece emerged from our collaboration.DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis material is based upon work supported by the National Science Foundation under Grant No. SES 2220631.
Deliberative Mini-Publics and Equity: Procedural Benefits and Promising Outcomes for Gene Editing
Authors: Naomi Scheinerman
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Public Engagement through Inclusive Deliberation: The Human Genome International Commission and Citizens' JuriesThis article refers to:The Promise and Reality of Public Engagement in the Governance of Human Genome Editing Research Additional informationFundingThis work was supported by National Human Genome Research Institute. Award number: 25T32HG009496.
The Intrinsic Value of Public Deliberation in the Governance of Human Genome Editing
Authors: Kalina Kamenova
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Promise and Reality of Public Engagement in the Governance of Human Genome Editing Research Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
STS and Bioethics: Forging New Synergies for Exploring the Potentials and Pitfalls of Public Engagement with New Biotechnologies
Authors: Ruth Müller, Amy Clare, Anja K. Ruess
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Promise and Reality of Public Engagement in the Governance of Human Genome Editing Research Additional informationFundingThis commentary builds on two recent research projects in which we studied issues of gene editing in livestock agriculture in Bavaria (FORTiGe) as well as issues of responsible and inclusive co-creation (SCALINGS). We would like to gratefully acknowledge the generous research support offered by the two funding agencies, the Bayerische Forschungsstiftung (FORTiGe) and the European Comission's Horizon 2020 Science with and for Society (SwafS) program through the SCALINGS project (Grant No. 788359).
Social Inequality and Human Genome Editing: A Nuanced Analysis of the <i>Ubuntuan</i> Ethical Prism
Authors: Michael O. S. Afolabi, Stephen Sodeke
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Promoting Equality in the Governance of Heritable Human Genome Editing through Ubuntu: Reflecting on a South African Public Engagement Study Additional informationFundingProf. Sodeke's research is partly funded by Grants U54 CA118948, U54MD007585, and 1UL1TR001417; respectively, from the National Cancer Institute (NCI), the National Institute on Minority Health and Health Disparities (NIMHD), and the National Center for Advancing Translational Sciences (NCATS).
Rethinking the “Public” and Rethinking “Engagement”
Authors: Brandy Fox, Daphne Oluwaseun Martschenko
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Promise and Reality of Public Engagement in the Governance of Human Genome Editing Research Additional informationFundingEffort for Brandy Fox was supported by grant T32HG008953.
Atorvastatin Does Not Attenuate Aortic Stiffening After Doxorubicin for Breast Cancer and Lymphoma (PREVENT-WF-98213)
Authors: Alexander R. Lucas, Ralph D’Agostino, Jennifer H. Jordan, Kerryn W. Reding, Nathaniel S. O’Connell, Giselle C. Melendez, Fadi N. Salloum, Kathryn E. Weaver, Glenn J. Lesser, W. Gregory Hundley
Journal: JACC CardioOncology (2023)
Cardioprotection in Patients at High Risk of Anthracycline-Induced Cardiotoxicity
Authors: Peter A. Henriksen, Stephen Rankin, Ninian N. Lang
Journal: JACC CardioOncology (2023)

A nthracyclines form the backbone of many chemotherapy protocols and are frequently used with curative intent in lymphoma, childhood leukemia, breast cancer, and other solid tumors.The potential for anthracycline-related myocardial injury and development of left ventricular (LV) dysfunction and heart failure (HF) remains a concern.This short-form primer will focus on the evidence for cardioprotection strategies to mitigate anthracycline cardiotoxicity in high-risk patients.
A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer
Authors: David Pook, Daniel M. Geynisman, Joan Carles, Filippo de Braud, Anthony M. Joshua, José Luis Pérez-Gracia, Casilda Llácer Pérez, Sang Joon Shin, Bruno Fang, Minal Barve, Marco Maruzzo, Sergio Bracarda, Miso Kim, Yannick Kerloeguen, Jorge Daniel Gallo, Sophia L. Maund, Adam Harris, Kuan-Chieh Huang, Victor Poon, Dhruvitkumar S. Sutaria, Howard Gurney
Journal: Clinical Cancer Research (2023)

To report the safety and efficacy of ipatasertib (AKT inhibitor) combined with rucaparib (PARP inhibitor) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with second-generation androgen receptor inhibitors.In this two-part phase Ib trial (NCT03840200), patients with advanced prostate, breast, or ovarian cancer received ipatasertib (300 or 400 mg daily) plus rucaparib (400 or 600 mg twice daily) to assess safety and identify a recommended phase II dose (RP2D). A part 1 dose-escalation phase was followed by a part 2 dose-expansion phase in which only patients with mCRPC received the RP2D. The primary efficacy endpoint was prostate-specific antigen (PSA) response (≥50% reduction) in patients with mCRPC. Patients were not selected on the basis of tumor mutational status.Fifty-one patients were enrolled (part 1 = 21; part 2 = 30). Ipatasertib 400 mg daily plus rucaparib 400 mg twice daily was the selected RP2D, received by 37 patients with mCRPC. Grade 3/4 adverse events occurred in 46% (17/37) of patients, with one grade 4 adverse event (anemia, deemed related to rucaparib) and no deaths. Adverse events leading to treatment modification occurred in 70% (26/37). The PSA response rate was 26% (9/35), and the objective response rate per Response Criteria in Solid Tumors (RECIST) 1.1 was 10% (2/21). Median radiographic progression-free survival per Prostate Cancer Working Group 3 criteria was 5.8 months [95% confidence interval (CI), 4.0-8.1], and median overall survival was 13.3 months (95% CI, 10.9-not evaluable).Ipatasertib plus rucaparib was manageable with dose modification but did not demonstrate synergistic or additive antitumor activity in previously treated patients with mCRPC.
Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor
Authors: Yuesheng Zhang
Journal: Pharmacological Reviews (2023)

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is activated by ligand binding, overexpression, or mutation. It is well known for its tyrosine kinase-dependent oncogenic activities in a variety of human cancers. A large number of EGFR inhibitors have been developed for cancer treatment, including monoclonal antibodies, tyrosine kinase inhibitors, and a vaccine. The EGFR inhibitors are aimed at inhibiting the activation or the activity of EGFR tyrosine kinase. However, these agents have shown efficacy only in a few types of cancers. Drug resistance, both intrinsic and acquired, is common even in cancers where the inhibitors have shown efficacy. The drug resistance mechanism is complex and not fully known. The key vulnerability of cancer cells that are resistant to EGFR inhibitors has not been identified. Nevertheless, it has been increasingly recognized in recent years that EGFR also possesses kinase-independent oncogenic functions and that these noncanonical functions may play a crucial role in cancer resistance to EGFR inhibitors. In this review, both kinase-dependent and -independent activities of EGFR are discussed. Also discussed are the mechanisms of actions and therapeutic activities of clinically used EGFR inhibitors, and sustained EGFR overexpression and EGFR interaction with other receptor tyrosine kinases to counter the EGFR inhibitors. Moreover, this review discusses emerging experimental therapeutics that have shown potential of overcoming the limitation of the current EGFR inhibitors in preclinical studies. The findings underscore the importance and feasibility of targeting both kinase-dependent and -independent functions of EGFR, to enhance therapeutic efficacy and minimize drug resistance. <b>Significance Statement</b> EGFR is a major oncogenic driver and therapeutic target, but cancer resistance to current EGFR inhibitors remains a significant unmet clinical problem. Here, I review the cancer biology of EGFR as well as the mechanisms of actions and the therapeutic efficacies of current and emerging EGFR inhibitors. The findings could potentially lead to development of more effective treatments for EGFR-positive cancers.
Critiquing the Critique of Advocacy
Authors: Ari Neeman
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Innovating for a Just and Equitable Future in Genomic and Precision Medicine ResearchThis article refers to:Rare Disease, Advocacy and Justice: Intersecting Disparities in Research and Clinical Care DISCLOSURE STATEMENTAri Ne'eman reports consulting income within the past twelve months from the Service Employees International Union, Inclusa, CareSource, and HHS Office for Civil Rights. The data presented here were not collected as part of his duties for any of the above entities, including HHS, and the research, analysis, findings, and conclusions were not reviewed by them nor do they necessarily represent their views.Additional informationFundingThis work was supported in part by the National Institute of Mental Health of the National Institutes of Health under Award Number T32MH019733. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
A Nonconserved Histidine Residue on KRAS Drives Paralog Selectivity of the KRASG12D Inhibitor MRTX1133
Authors: Miles A. Keats, John J.W. Han, Yeon-Hwa Lee, Chih-Shia Lee, Ji Luo
Journal: Cancer Research (2023)

Abstract MRTX1133 is the first noncovalent inhibitor against the KRASG12D mutant that demonstrated specificity and potency in preclinical tumor models. Here, we used isogenic cell lines expressing a single RAS allele to evaluate the selectivity of this compound. In addition to KRASG12D, MRTX1133 showed significant activity against several other KRAS mutants as well as wild-type KRAS protein. In contrast, MRTX1133 exhibited no activity against both G12D and wild-type forms of HRAS and NRAS proteins. Functional analysis revealed that the selectivity of MRTX1133 toward KRAS is associated with its binding to H95 on KRAS, a residue that is not conserved in HRAS and NRAS. Reciprocal mutation of amino acid 95 among the three RAS paralogs resulted in reciprocal change in their sensitivity toward MRTX1133. Thus, H95 is an essential selectivity handle for MRTX1133 toward KRAS. Amino acid diversity at residue 95 could facilitate the discovery of pan-KRAS inhibitors as well as HRAS and NRAS paralog-selective inhibitors. Significance: The nonconserved H95 residue on KRAS is required for the selectivity of the KRASG12D inhibitor MRTX1133 and can be exploited for the development of pan-KRAS inhibitors.
Tipifarnib Potentiates the Antitumor Effects of PI3Kα Inhibition in<i>PIK3CA</i>- and<i>HRAS</i>-Dysregulated HNSCC via Convergent Inhibition of mTOR Activity
Authors: Alison E. Smith, Stacia Chan, Zhiyong Wang, Asako McCloskey, Quinn Reilly, Jayden Z. Wang, Hetika Vora Patel, Keiichi Koshizuka, Harris S. Soifer, Linda Kessler, Ashley Dayoub, Victoria Villaflor, Douglas R. Adkins, Justine Y. Bruce, Alan L. Ho, Cesar A. Perez, Glenn J. Hanna, Amaya Gascó Hernández, Andrew Saunders, Stephen Dale, J. Silvio Gutkind, Francis Burrows, Shivani Malik
Journal: Cancer Research (2023)

Abstract Outcomes for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are poor, with median overall survival (OS) ranging from 6 to 18 months. For those who progress on standard-of-care (chemo)immunotherapy, treatment options are limited, necessitating the development of rational therapeutic strategies. Toward this end, we targeted the key HNSCC drivers PI3K–mTOR and HRAS via the combination of tipifarnib, a farnesyltransferase (FTase) inhibitor, and alpelisib, a PI3Kα inhibitor, in multiple molecularly defined subsets of HNSCC. Tipifarnib synergized with alpelisib at the level of mTOR in PI3Kα- or HRAS-dependent HNSCCs, leading to marked cytotoxicity in vitro and tumor regression in vivo. On the basis of these findings, the KURRENT-HN trial was launched to evaluate the effectiveness of this combination in PIK3CA-mutant/amplified and/or HRAS-overexpressing R/M HNSCC. Preliminary evidence supports the clinical activity of this molecular biomarker-driven combination therapy. Combined alpelisib and tipifarnib has potential to benefit &amp;gt;45% of patients with R/M HNSCC. By blocking feedback reactivation of mTORC1, tipifarnib may prevent adaptive resistance to additional targeted therapies, enhancing their clinical utility. Significance: The mechanistically designed, biomarker-matched strategy of combining alpelisib and tipifarnib is efficacious in PIK3CA- and HRAS-dysregulated head and neck squamous carcinoma and could improve outcomes for many patients with recurrent, metastatic disease. See related commentary by Lee et al., p. 3162